We propose to utilize the membrane active properties of amphotericin B and other agents to try to circumvent selectively the permeability barrier of malignant cells and increase the uptake and thereby the effectiveness of inhibitors of macromolecular synthesis. On the basis of our previous experiments and some recent work from other laboratories, the following studies are proposed: A. Screening for membrane active agents effective in increasing permeabiliy of yeast and animal cells to other drugs and macromolecules. B. Determination of the selectivity of the membrane active agents and the inhibitors of macromolecular synthesis. C. Exploration of the use of yeast and other fungi as models for relevant effects of macromolecular synthesis and breakdown in animal cells. D. Testing the synergy hypothesis against animal tumors.